The oncogenic human adenoviruses are powerful systems to understand human cell function, and especially the mechanisms of cell transformation. Human adenoviruses form three oncogenic groups that differ completely in transforming gene sequences. We propose to first rigorously identify the protein products of the transforming genes of the three oncogenic groups. Our long range goals are to purify the transforming proteins to homogeneity, and to study their physicochemical and biological properties. We will then investigate how these prolactins function in cell transformation and virus replication. We hope to establish whether the three group types of transforming proteins (1) have the same functions in cell transformation, (2) have different functions but transform cells by the same basic mechanism (e.g. initiation of host cell DNA replication), or (3) have three distinct functions and transform cells by three distinct mechanisms. Success in these studies will greatly increase our understanding of neoplastic transformation and growth control. The practical benefits that derive from understanding the functions of adenovirus transforming proteins are potentially enormous. The adenovirus replication machinery is a composite of both viral and host coded enzymes. Thus by determining transforming proteins function in viral gene expression and replication, we may learn how analogous processes are regulated by human cells. Such basic information is fundamental to the development of reagents and procedures to control cancer and other cellular diseases. Human adenoviruses are ubiquitous, and it is possible that they may play an etiological role in human cancer. Our program may assist in evaluating this possibility, and in combatting human cancer.